The present invention relates to multi-dimensional image reconstruction and analysis, and more particularly, but not exclusively to such image reconstruction of radioactive source or sources, directed to expert-system diagnosis.
Radionuclide imaging aims at obtaining an image of a radioactively labeled substance, that is, a radiopharmaceutical, within the body, following administration, generally, by injection. The substance is chosen so as to be picked up by active pathologies to a different extent from the amount picked up by the surrounding healthy tissue; in consequence, the pathologies are operative as radioactive-emission sources and may be detected by radioactive-emission imaging. A location of pathology may appear as a concentrated source of high radiation, that is, a hot region, as may be associated with a tumor, or as a region of low-level radiation, which is nonetheless above the background level, as may be associated with carcinoma.
A reversed situation is similarly possible. Dead tissue has practically no pick up of radiopharmaceuticals, and is thus operative as a cold region.
The mechanism of localization of a radiopharmaceutical in a particular organ of interest depends on various processes in the organ of interest such as antigen-antibody reactions, physical trapping of particles, receptor-site binding, removal of intentionally damaged cells from circulation, and transport of a chemical species across a cell membrane and into the cell by a normally operative metabolic process.
The particular choice of a radionuclide for labeling antibodies depends upon the chemistry of the labeling procedure and the isotope nuclear properties, such as the number of gamma rays emitted, their respective energies, the emission of other particles such as beta or positrons, the isotope half-life, and the decay scheme.
In PET imaging, positron emitting radio-isotopes are used for labeling, and the imaging camera detects coincidence photons, the gamma pair of 0.511 Mev, traveling in opposite directions. Each coincidence detection defines a line of sight, along which annihilation takes place. As such, PET imaging collects emission events, which occurred in an imaginary tubular section enclosed by the PET detectors. A gold standard for PET imaging is PET NH3 rest myocardial perfusion imaging with N-13-ammonia (NH3), at a dose level of 740 MBq, with attenuation correction. Yet, since the annihilation gamma is of 0.511 Mev, regardless of the radio-isotope, PET imaging does not provide spectral information, and does not differentiate between radio-isotopes.
In SPECT imaging, primarily gamma emitting radio-isotopes are used for labeling, and the imaging camera is designed to detect the actual gamma emission, generally, in an energy range of approximately 11-511 KeV. Generally, each detecting unit, which represents a single image pixel, has a collimator that defines the solid angle from which radioactive emission events may be detected.
Because PET imaging collects emission events, in the imaginary tubular section enclosed by the PET detectors, while SPECT imaging is limited to the solid collection angles defined by the collimators, generally, PET imaging has a higher sensitivity and spatial resolution than does SPECT. Therefore, the gold standard for spatial and time resolutions in nuclear imaging is defined for PET.
The radiopharmaceutical behavior in vivo is a dynamic process. Some tissues absorb radiopharmaceuticals faster than others or preferentially to others, and some tissues flush out the radiopharmaceuticals faster than others or preferentially to others, so the relative darkness of a given tissue is related to a time factor. Since the uptake clearance of such a radiopharmaceutical by the various tissues (target and background) varies over time, standard diagnosis protocols usually recommend taking an image at the time at which the ratio of target emission versus background emission is the highest.
Yet, this approach produces a single parameter per voxel of the reconstructed image, a level of gray, at a specific time, and ignores the information that could be obtained from the behavior of a radiopharmaceutical as a function of time.
Dynamic imaging, on the other hand, attempts to acquire the behavior of a radiopharmaceutical as a function of time, for example, to measure perfusion in myocardial tissue. Dynamic imaging is advantageous to static imaging, as it provides a better measure of blood flow, it is more sensitive to ischemia than static imaging, and both perfusion and myocardial viability may be obtained from a single imaging session.
Garcia et al. (Am. J. Cardiol. 51st Annual Scientific Session, 2002) describe a dynamic SPECT acquisition, using Tc-99m-teboroxime as a myocardial perfusion tracer. Dual, 90° detectors were fanned 180° every 36 seconds, for up to 4 minutes. All the fanned projections were mathematically combined to yield a “static” acquisition to reduce artifacts by accounting for both changing myocardial concentration and increasing liver activity. The purpose of the investigation was to test the quality and accuracy of images from this protocol.
Ronald H. Huesmany, Bryan W. Reuttery, G. Larry Zengz and Grant T. Gullberg (Kinetic Parameter Estimation from SPECT Cone-Beam Projection Measurements, 1997 International Meeting on Fully 3-D Image Reconstruction Conference Record, pages 121-125) describe a method for obtaining radiopharmaceutical kinetic parameters from SPECT. The kinetic parameters are commonly estimated from dynamically acquired nuclear medicine data by reconstructing a dynamic sequence of images and subsequently fitting the parameters to time activity curves generated from regions of interest overlaid upon the reconstructed image sequence. Since SPECT data acquisition involves movement of the detectors, and the distribution of radiopharmaceutical changes during the acquisition, the image reconstruction step can produce erroneous results that lead to biases in the estimated kinetic parameters. If the SPECT data are acquired using cone-beam collimators, wherein the gantry rotates so that the focal point of the collimators always remains in a plane, the additional problem of reconstructing dynamic images from insufficient projection samples arises. The reconstructed intensities will also have errors due to insufficient acquisition of cone-beam projection data, thus producing additional biases in the estimated kinetic parameters.
To overcome these problems, the authors investigated the estimation of the kinetic parameters directly from the projection data by modeling the data acquisition process of a time-varying distribution of radiopharmaceutical detected by a rotating SPECT system with cone-beam collimation. To accomplish this it was necessary to parameterize the spatial and temporal distribution of the radiopharmaceutical within the SPECT cone-beam field of view. The authors hypothesized that by estimating directly from cone-beam projections instead of from reconstructed time-activity curves, the parameters which describe the time-varying distribution of radiopharmaceutical could be estimated without bias.
In a private communication, on Nov. 2, 2005, Gullberg reports:                “In the 90s we had some success with obtaining measurements of flow-times-extraction and distribution volume with dynamic SPECT using the radiopharmaceutical Tc-99m-teboroxime. This agent has a fast washin and washout from the myocardial tissue. A 3 detector PRISM 300XP SPECT system (Picker) was able to acquire 128×128×120 views ever 5 seconds. This gave good timing resolution but the photon statistics were low even with an injection of 20 to 30 mCi of 99mTc-teboroxime. However, even with these low statistics, one was able to show improved contrast for lesion detection as compared with static imaging using 201Tl. Also, one was able to obtain values of coronary flow reserve; however, these values were lower than the gold standard of dynamic PET using 13NH3. The low statistics produced bias in our estimates of flow-times-extraction and increased the variance in the estimated parameters, especially for the nonlinear parameter that measured the washout from the tissue. The detector efficiency and speed of rotation limits the photon yield and timing resolution for measuring a dynamic agent. The SPECT systems of today have moved away from systems that can acquire any type of dynamic data. These are large rotating gamma cameras that are designed to perform static cardiac SPECT and whole body imaging in a single system. The timing resolution is very poor, approximately 14 seconds as compared with our previous 5 seconds. Added to this is the fact that good flow agents such as 99mTc-teboroxime are no longer on the market because these systems cannot adequately image the fast turnover in the tissue.”        
Multiple-isotopes analysis is known. For example, U.S. Pat. No. 5,249,124, to DeVito, issued on September 1993, “Multi-isotope imaging using energy-weighted acquisition for, e.g., myocardial perfusion studies,” describes a study, carried out imaging a plurality of imaging agents, simultaneously. The information obtained was weighted using as many energy weighting functions as there were isotopes. The weighting reduces “crosstalk” between each of the single-isotope images, thus producing improved results, for example, in dual-isotope (Tc-99m and Tl-201) myocardial perfusion studies.
Radiopharmaceutical imaging, while providing functional information regarding tissue viability and function, provides little structural information. In essence, two types of medical images may be distinguished:    1. functional body images, such as may be produced by gamma camera, SPECT, and PET scans, after the injection of a radiopharmaceutical, to provide physiological information; and    2. structural images, such as may be produced by as x-ray, CT, ultrasound, and (or) MRI scans, to provide anatomic, or structural maps of the body, for example, by distinguishing bones, fat, and muscle tissue.
Techniques for registering functional and structural images on a same system of coordinates, to produce a combined or fused image, are known, and are disclosed, for example in the publication to D. A. Weber and M. Ivanovic, “Correlative image registration”, Sem. Nucl. Med., vol. 24 pp. 311-323 (1994), as well as in K. Kneöaurek, M. Ivanovic, J. Machac, and D. A. Weber, “Medical image registration,” Europhysics News (2000) Vol. 31 No. 4, in U.S. Pat. No. 6,212,423, to Krakovitz, dated, Apr. 3, 2001, and entitled Diagnostic hybrid probes, in U.S. Pat. No. 5,672,877, to Liebig, et al., dated Sep. 30, 1997 and entitled, “Coregistration of multi-modality data in a medical imaging system,” in U.S. Pat. No. 6,455,856, to Gagnon, dated, Sep. 24, 2002 and entitled, “Gamma camera gantry and imaging method,” and in commonly owned U.S. Pat. No. 6,567,687, to Front et al., issued on May 20, 2003, and entitled, “Method and system for guiding a diagnostic or therapeutic instrument towards a target region inside the patient's body,” all of whose disclosures are incorporated herein by reference.
These techniques may be used, for example, in order to identify features seen on the functional map, based on their anatomic location in the structural map.
Additionally, they may be used to provide attenuation correction to the radiopharmaceutical image. Attenuation refers to the loss of information due to the interaction of emitted photons with matter, through photon absorption by the photoelectric effect, photon scatter by the Compton effect, and pair production involving photons of energies greater than 1.02 Mev. Attenuation decreases the number of photon counts from that which would have been recorded in vacuum.
Various methods of attenuation corrections are known.
Emission-transmission imaging combines anatomical (structural) information from x-ray transmission images with physiological (functional) information from radiopharmaceutical emission images. By correlating the emission and transmission images, an observer may identify and delineate the location of the radiopharmaceutical source. In addition, the quantitative accuracy of measurement of radiopharmaceutical source is improved through use of iterative reconstruction methods.
For example, PCT Application PCT/US90/03722, to Kaplan, describes an emission-transmission system in which the emission data from a radiopharmaceutical to and transmission data from an x-ray source are acquired with the same detector (single or multiple heads). An alternative emission-transmission imaging system, disclosed in SU-1405-819-A, uses x-ray transmission data and two detectors for determining the direction of the photons to improve detection efficiency. However, an exact method of correcting emission data based on transmission data is not described by either Kaplan or in SU-1405-819-A.
Commonly owned PCT Publication WO2004/042546, whose disclosure is incorporated herein by reference, describes systems for radiopharmaceutical or x-ray imaging, with attenuation correction by another modality, of a completely different nature, for example, MRI or ultrasound, thus avoiding the iterative process when correcting emission information by transmission information—both being information of similar nature. PCT Publication WO2004/042546 describes a system comprising, a first device, for obtaining a first image, by a first modality, such as gamma scan or x-ray, a second device, for obtaining a second, structural image, by a second modality, such as MRI or ultrasound, and a computerized system, configured to display an attenuation-corrected first image and a superposition of the attenuation-corrected first image and the second, structural image. Furthermore, the system is operative to guide an in-vivo instrument based on the superposition.